Is BRCA2 p.Asn1742Ter (c.5223dup) pathogenic?

BRCA2 p.Asn1742Ter (c.5223dup) is classified Likely pathogenic in BRCA2 (ClinVar, Single submitter, 2 submitters; last evaluated 2021-10-19). Absent from gnomAD; Associated with hereditary breast carcinoma.

What condition is associated with BRCA2 p.Asn1742Ter (c.5223dup)?

BRCA2 p.Asn1742Ter (c.5223dup) is associated with hereditary breast carcinoma, breast-ovarian cancer, familial, susceptibility to, 2 (ClinVar).

How common is BRCA2 p.Asn1742Ter (c.5223dup) in the general population?

BRCA2 p.Asn1742Ter (c.5223dup) is absent from gnomAD (gnomAD).

How is Hereditary breast cancer inherited?

Typically Autosomal dominant, Multigenic/multifactorial (Orphanet). A genetic counselor can assess individual risk for a family.

BRCA2 p.Asn1742Ter

c.5223dup · rs1555284120 · VCV487425

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

hereditary breast carcinoma

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 11 of 27
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.44	GERP -2.3, phastCons 0.78

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: BRCA2
Protein: p.Asn1742Ter
Coding: c.5223dup
MANE Select: NM_000059
dbSNP: rs1555284120
Type: Duplication
Location: chr13:32339577 (GRCh38)
Gene constraint: LOEUF 0.803 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 1742: the 'interaction with rad51' region; the 'interaction with polh' region

Full BRCA2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hereditary breast carcinoma — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: breast-ovarian cancer, familial, susceptibility to, 2

For Hereditary breast cancer (Orphanet):

Inheritance: Autosomal dominant, Multigenic/multifactorial
Onset: Adult, Elderly

Similar variants

BRCA2 p.Asn1742_Ser1743del Conflicting classifications of pathogenicity ★ same residue
BRCA2 p.Asn1742Ile Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA2 c.1448_1451dupCAGT Pathogenic ★★★ same condition
BRCA2 c.6081dupA Pathogenic ★★★ same condition
BRCA2 c.6396dupA Pathogenic ★★★ same condition
BRCA2 c.6528_6535dup Pathogenic ★★★ same condition
BRCA2 c.7806-2_7806-1dup Pathogenic ★★★ same condition
BRCA2 n.6325_6326insT Pathogenic ★★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/brca2-p-asn1742ter (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown